It is now well recognized that obesity is a major public health concern, and its prevalence has tremendously increased worldwide over the last decades, including Tunisia. As obesity is associated with cardiovascular diseases, the purpose of this study was to investigate the effect of obesity on forearm skin blood flow (FSBF) response to acetylcholine (Ach), an endothelium-dependent vasodilator, in Tunisian women over a wide range of body mass indices (BMIs). One hundred and eighty healthy women with an average age of 34+/-6 years, an average height of 162+/-7 cm and an average weight of 78+/-19 kg participated in this investigation. The mean BMIs of the 60 lean, 50 overweight and 70 obese subjects were 22.1+/-0.3, 27.7+/-0.2 and 38.4+/-0.7 kg m(-2), respectively. The FSBF was measured non-invasively using a laser Doppler flowmeter in response to local infusion of a cumulative dose of Ach. After adjusting for age, the mean response of FSBF to Ach was significantly greater in lean (1168%+/-78) than in overweight (643%+/-38) and obese subjects (323%+/-18) (P=0.002; P<0.0001, respectively), suggesting a reduction of the endothelium-dependent nitric oxide (NO) release by obesity. Our regression analysis also revealed that the maximum FSBF response to Ach (that is, its efficacy) was inversely correlated with BMI, waist and hip circumferences (r=-0.994, P=0.002; r=-0.2, P<0.0001, and r=-0.321, P=0.001, respectively). Our data demonstrate a reduction of skin vasodilatory reserve in obese patients and suggest a defect of both endothelial-dependent relaxation and wall compliance associated with obesity.